Dr Muhammad Jamaluddin

Dr Muhammad Jamaluddin

Research Assistant

School of Biomedical Sciences and Pharmacy

Career Summary

Biography

I graduated with a degree double majoring in Biomedical Sciences and Microbiology and first class honours in Microbiology from the University of Queensland (UQ), Australia. I was awarded UQ international postgraduate research scholarship in 2011 to pursue my doctoral studies specializing in Protein Biochemistry at the School of Chemistry Molecular Biosciences, UQ. During my doctoral studies, I learnt and developed new methodologies in glycoproteomics in Dr Benjamin Schulz lab (NHMRC Career Development Fellow). In 2016, I joined Dr Pradeep Tanwar lab (ARC Future Fellow, Cancer Institute NSW Career Development Fellow and international leader on gynaecological cancer research) at the School of Biomedical Sciences and Pharmacy, the University of Newcastle, Australia. I am an early career researcher and was recently awarded with a John Hunter Hospital Charitable Trust project grant 2017 to advance my project. The major focus is to explore the mechanistic function of extracellular matrix in uterine leiomyogenesis.

Qualifications

  • PhD (Biochemistry), University of Queensland

Keywords

  • Medical Biochemistry
  • Proteomics
  • Glycosylation
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Publications

For publications that are currently unpublished or in-press, details are shown in italics.


Journal article (10 outputs)

Year Citation Altmetrics Link
2018 Ko YA, Jamaluddin MFB, Adebayo M, Bajwa P, Scott RJ, Dharmarajan AM, et al., 'Extracellular matrix (ECM) activates ß-catenin signaling in uterine fibroids', Reproduction, 155 61-71 (2018) [C1]

© 2018 Society for Reproduction and Fertility. Recent studies showed that genetic aberrations in the MED12 gene, probably through the canonical WNT/ß-catenin pathway, lead to the ... [more]

© 2018 Society for Reproduction and Fertility. Recent studies showed that genetic aberrations in the MED12 gene, probably through the canonical WNT/ß-catenin pathway, lead to the pathogenesis of uterine fibroids. However, a comprehensive analysis of the WNT pathway in MED12-mutated and MED12-wildtype fibroids has not been performed. The objective of this study was to determine the status of the WNT pathway in human fibroids. We performed Sanger sequencing to define the MED12 mutational status of fibroids and normal myometrium samples. qPCR arrays were carried out to determine the status of the WNT signaling pathway in MED12-mutated and MED12-wild-type fibroids. Liquid chromatography-mass spectrometry (LC-MS), Western blotting and immunohistochemistry were used to monitor the expression of ß-catenin. We showed that ß-catenin expression was increased in fibroids compared to the adjacent myometrium samples. However, ß-catenin expression showed no correlation with MED12 mutation status. Of all the WNT signaling components, WNT inhibitors showed the greatest differences in expression between fibroids and controls. WIF1, a WNT inhibitor, was identified as the most significantly upregulated gene in fibroids. We cultured primary fibroid cells on hydrogels of known stiffness to decipher the influence of biomechanical cues on ß-catenin expression and revealed increased levels of ß-catenin when cells were cultured on a stiffer surface. In conclusion, our data showed that ß-catenin expression in fibroids occurs independently of MED12 mutations. Biomechanical changes upregulate ß-catenin expression in fibroids, providing an attractive avenue for developing new treatments for this disease.

DOI 10.1530/REP-17-0339
Citations Web of Science - 1
Co-authors Rodney Scott, Pradeep Tanwar
2018 Jamaluddin MFB, Nagendra PB, Nahar P, Oldmeadow C, Tanwar PS, 'Proteomic Analysis Identifies Tenascin-C Expression Is Upregulated in Uterine Fibroids.', Reprod Sci, 1933719118773420 (2018)
DOI 10.1177/1933719118773420
Co-authors Christopher Oldmeadow, Pradeep Tanwar
2018 Goad J, Ko Y-A, Kumar M, Jamaluddin MFB, Tanwar PS, 'Oestrogen fuels the growth of endometrial hyperplastic lesions initiated by overactive Wnt/ß-catenin signalling.', Carcinogenesis, (2018)
DOI 10.1093/carcin/bgy079
Co-authors Pradeep Tanwar
2018 Jamaluddin MFB, Nahar P, Tanwar PS, 'Proteomic Characterization of the Extracellular Matrix of Human Uterine Fibroids.', Endocrinology, 159 2656-2669 (2018)
DOI 10.1210/en.2018-00151
Co-authors Pradeep Tanwar
2018 Jamaluddin MFB, Ko YA, Kumar M, Brown Y, Bajwa P, Nagendra PB, et al., 'Proteomic profiling of human uterine fibroids reveals upregulation of the extracellular matrix protein periostin', Endocrinology, 159 1106-1118 (2018) [C1]

Copyright © 2018 Endocrine Society The central characteristic of uterine fibroids is excessive deposition of extracellular matrix (ECM), which contributes to fibroid growth and bu... [more]

Copyright © 2018 Endocrine Society The central characteristic of uterine fibroids is excessive deposition of extracellular matrix (ECM), which contributes to fibroid growth and bulk-type symptoms. Despite this, very little is known about patterns of ECM protein expression in fibroids and whether these are influenced by the most common genetic anomalies, which relate to MED12. We performed extensive genetic and proteomic analyses of clinically annotated fibroids and adjacent normal myometrium to identify the composition and expression patterns of ECM proteins in MED12 mutation-positive and mutation-negative uterine fibroids. Genetic sequencing of tissue samples revealed MED12 alterations in 39 of 65 fibroids (60%) from 14 patients. Using isobaric tagged-based quantitative mass spectrometry on three selected patients (n = 9 fibroids), we observed a common set of upregulated (.1.5-fold) and downregulated (,0.66-fold) proteins in small, medium, and large fibroid samples of annotated MED12 status. These two sets of upregulated and downregulated proteins were the same in all patients, regardless of variations in fibroid size and MED12 status. We then focused on one of the significant upregulated ECM proteins and confirmed the differential expression of periostin using western blotting and immunohistochemical analysis. Our study defined the proteome of uterine fibroids and identified that increased ECM protein expression, in particular periostin, is a hallmark of uterine fibroids regardless of MED12 mutation status. This study sets the foundation for further investigations to analyze the mechanisms regulating ECM overexpression and the functional role of upregulated ECM proteins in leiomyogenesis.

DOI 10.1210/en.2017-03018
Citations Scopus - 1Web of Science - 1
Co-authors Hubert Hondermarck, Pradeep Tanwar, Rodney Scott, Mark Baker, Matt Dun, Manishkumar Jhamb
2014 Jamaluddin MFB, Bailey UM, Schulz BL, 'Oligosaccharyltransferase subunits bind polypeptide substrate to locally enhance N-glycosylation', Molecular and Cellular Proteomics, 13 3286-3293 (2014)

© 2014 by The American Society for Biochemistry and Molecular Biology, Inc. Oligosaccharyltransferase is a multiprotein complex that catalyzes asparagine-linked glycosylation of d... [more]

© 2014 by The American Society for Biochemistry and Molecular Biology, Inc. Oligosaccharyltransferase is a multiprotein complex that catalyzes asparagine-linked glycosylation of diverse proteins. Using yeast genetics and glycoproteomics, we found that transient interactions between nascent polypeptide and Ost3p/Ost6p, homologous subunits of oligosaccharyltransferase, were able to modulate glycosylation efficiency in a site-specific manner in vivo. These interactions were driven by hydrophobic and electrostatic complementarity between amino acids in the peptidebinding groove of Ost3p/Ost6p and the sequestered stretch of substrate polypeptide. Based on this dependence, we used in vivo scanning mutagenesis and in vitro biochemistry to map the precise interactions that affect site-specific glycosylation efficiency. We conclude that transient binding of substrate polypeptide by Ost3p/Ost6p increases glycosylation efficiency at asparagines proximal and C-terminal to sequestered sequences. We detail a novel mode of interaction between translocating nascent polypeptide and oligosaccharyltransferase in which binding to Ost3p/Ost6p segregates a short flexible loop of glycosylation-competent polypeptide substrate that is delivered to the oligosaccharyltransferase active site for efficient modification.

DOI 10.1074/mcp.M114.041178
Citations Scopus - 9Web of Science - 9
2014 Tan NY, Bailey UM, Jamaluddin MF, Mahmud SHB, Raman SC, Schulz BL, 'Sequence-based protein stabilization in the absence of glycosylation', Nature Communications, 5 (2014)

Asparagine-linked N-glycosylation is a common modification of proteins that promotes productive protein folding and increases protein stability. Although N-glycosylation is import... [more]

Asparagine-linked N-glycosylation is a common modification of proteins that promotes productive protein folding and increases protein stability. Although N-glycosylation is important for glycoprotein folding, the precise sites of glycosylation are often not conserved between protein homologues. Here we show that, in Saccharomyces cerevisiae, proteins upregulated during sporulation under nutrient deprivation have few N-glycosylation sequons and in their place tend to contain clusters of like-charged amino-acid residues. Incorporation of such sequences complements loss of in vivo protein function in the absence of glycosylation. Targeted point mutation to create such sequence stretches at glycosylation sequons in model glycoproteins increases in vitro protein stability and activity. A dependence on glycosylation for protein stability or activity can therefore be rescued with a small number of local point mutations, providing evolutionary flexibility in the precise location of N-glycans, allowing protein expression under nutrient-limiting conditions, and improving recombinant protein production. © 2014 Macmillan Publishers Limited. All rights reserved.

DOI 10.1038/ncomms4099
Citations Scopus - 12Web of Science - 12
2013 Mohd Yusuf SNH, Bailey UM, Tan NY, Jamaluddin MF, Schulz BL, 'Mixed disulfide formation in vitro between a glycoprotein substrate and yeast oligosaccharyltransferase subunits Ost3p and Ost6p', Biochemical and Biophysical Research Communications, 432 438-443 (2013)

Oligosaccharyltransferase (OTase) glycosylates selected asparagine residues in secreted and membrane proteins in eukaryotes, and asparagine (N)-glycosylation affects the folding, ... [more]

Oligosaccharyltransferase (OTase) glycosylates selected asparagine residues in secreted and membrane proteins in eukaryotes, and asparagine (N)-glycosylation affects the folding, stability and function of diverse glycoproteins. The range of acceptor protein substrates that are efficiently glycosylated depends on the action of several accessory subunits of OTase, including in yeast the homologous proteins Ost3p and Ost6p. A model of Ost3p and Ost6p function has been proposed in which their thioredoxin-like active site cysteines form transient mixed disulfide bonds with cysteines in substrate proteins to enhance the glycosylation of nearby asparagine residues. We tested aspects of this model with a series of in vitro assays. We developed a whole protein mixed disulfide interaction assay that showed that Ost6p could form mixed disulfide bonds with selected cysteines in pre-reduced yeast Gas1p, a model glycoprotein substrate of Ost3p and Ost6p. A complementary peptide affinity chromatography assay for mixed disulfide bond formation showed that Ost3p could also form mixed disulfide bonds with cysteines in selected reduced tryptic peptides from Gas1p. Together, these assays showed that the thioredoxin-like active sites of Ost3p and Ost6p could form transient mixed disulfide bonds with cysteines in a model substrate glycoprotein, consistent with the function of Ost3p and Ost6p in modulating N-glycosylation substrate selection by OTase in vivo. © 2013 Elsevier Inc.

DOI 10.1016/j.bbrc.2013.01.128
Citations Scopus - 10Web of Science - 9
2012 Bailey U-M, Jamaluddin MF, Schulz BL, 'Analysis of Congenital Disorder of Glycosylation-Id in a Yeast Model System Shows Diverse Site-Specific Under-glycosylation of Glycoproteins', JOURNAL OF PROTEOME RESEARCH, 11 5376-5383 (2012)
DOI 10.1021/pr300599f
Citations Scopus - 29Web of Science - 30
2011 Jamaluddin MFB, Bailey U-M, Tan NYJ, Stark AP, Schulz BL, 'Polypeptide binding specificities of Saccharomyces cerevisiae oligosaccharyltransferase accessory proteins Ost3p and Ost6p', PROTEIN SCIENCE, 20 849-855 (2011)
DOI 10.1002/pro.610
Citations Scopus - 17Web of Science - 18
Show 7 more journal articles

Conference (1 outputs)

Year Citation Altmetrics Link
2017 Yi-An K, Jamaluddin M, Tanwar PS, 'Extracellular Matrix (ECM) and Wnt signalling nexus in human uterine leiomyomas', Perth (2017)
Co-authors Pradeep Tanwar
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Grants and Funding

Summary

Number of grants 2
Total funding $37,307

Click on a grant title below to expand the full details for that specific grant.


20181 grants / $17,307

Periostin as a biomarker in the diagnosis and surveillance of uterine leiomyomas$17,307

Funding body: John Hunter Hospital Charitable Trust

Funding body John Hunter Hospital Charitable Trust
Project Team Doctor Muhammad Jamaluddin, Associate Professor Pradeep Tanwar, Doctor Pravin Nahar
Scheme Research Grant
Role Lead
Funding Start 2018
Funding Finish 2018
GNo G1800008
Type Of Funding C3112 - Aust Not for profit
Category 3112
UON Y

20171 grants / $20,000

Mediator complex subunit 12 (MED12) gene in pathogenesis of uterine smooth muscle tumours$20,000

Funding body: John Hunter Hospital Charitable Trust

Funding body John Hunter Hospital Charitable Trust
Project Team Doctor Muhammad Jamaluddin, Associate Professor Pradeep Tanwar, Doctor Pravin Nahar
Scheme Research Grant
Role Lead
Funding Start 2017
Funding Finish 2017
GNo G1700368
Type Of Funding C3112 - Aust Not for profit
Category 3112
UON Y
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Dr Muhammad Jamaluddin

Position

Research Assistant
School of Biomedical Sciences and Pharmacy
Faculty of Health and Medicine

Contact Details

Email muhammad.jamaluddin@newcastle.edu.au
Phone (02) 4921 7476
Links Google+
Research Networks
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